OBJECTIVE To describe a case of a delayed-type hypersensitivity (DTH) reaction to piperacillin/tazobactam in which painful paresthesiae were a predominant feature. METHODS A 27-year-old man with a history of intravenous drug abuse was admitted for treatment of a pulmonary parenchymal abscess in the setting of lower-limb deep-venous thrombosis and methicillin-sensitive Staphylococcus aureus bacteremia. He was treated with intravenous piperacillin/tazobactam 4.5 g 3 times daily; however, after 2 weeks of therapy, he developed symptoms (eg, fever, chills) and laboratory abnormalities (eg, white blood cell count 2.1 x 10(3)/mm3, erythrocyte sedimentation rate 63 mm/h) suggestive of a DTH reaction. This was accompanied by infusion-related painful paresthesiae. The symptoms and laboratory abnormalities resolved within 48 hours of treatment being switched to flucloxacillin. CONCLUSIONS Due to the close temporal association and the absence of any other obvious explanation, we believe these paresthesiae represent an additional feature of the DTH reaction to piperacillin/tazobactam in this patient. Use of the Naranjo probability scale indicated a probable relationship between the paresthesiae and administration of piperacillin/tazobactam. CONCLUSIONS To our knowledge, as of March 24, 2006, this is the first case in which a DTH reaction to piperacillin/tazobactam manifesting as fever, neutropenia, and thrombocytopenia has been associated with paresthesiae.